Blunted response to systemic nitric oxide synthase inhibition in the cerebral circulation of patients with Type 2 diabetes

• Published in: Diabetic medicine 2006-04, Vol.23 (4), p.398-402
• Main Authors: Nazir, F. S., Alem, M., Small, M., Con Nell, J. M. C., Lees, K. R., Walters, M. R., Cleland, S. J.
• Format: Article
• Language: English
• Subjects: Adult; Area Under Curve; Biological and medical sciences; Carotid Arteries - diagnostic imaging; Carotid Arteries - physiopathology; Case-Control Studies; cerebral blood flow; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diagnostic imaging; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; endothelial dysfunction; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Humans; Infusions, Intravenous; Male; Medical sciences; Middle Aged; nitric oxide; nitric oxide synthase; Nitric Oxide Synthase - antagonists & inhibitors; omega-N-Methylarginine - pharmacology; Regional Blood Flow - drug effects; Risk; Stroke - etiology; Type 2 diabetes; Ultrasonography, Doppler, Transcranial - drug effects
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2006.01815.x

Aims  Diabetes is a major risk factor for stroke, but the mechanisms that impart the excess risk are unclear. Endothelial dysfunction, which has been demonstrated in the coronary and peripheral vasculature of diabetic patients, is an important early marker of vascular disease. However, the effect of diabetes on cerebrovascular endothelium has not been examined. We sought to investigate the effect of diabetes on basal cerebrovascular endothelial function as assessed by response to the nitric oxide synthase (NOS) inhibitor NG‐monomethyl‐l‐arginine (l‐NMMA). Methods  Fourteen men with Type 2 diabetes and 15 age‐matched male control subjects were recruited. The participants had no clinically evident vascular disease and were taking no vasoactive or lipid‐lowering medication. Each received a single 15‐min intravenous infusion of l‐NMMA (0.8 mol/kg/min). Cerebral blood flow was assessed by colour Doppler imaging of the internal carotid artery (ICA) at 10‐min intervals for 20 min prior to and following the infusion. Middle cerebral artery velocity (MCAv) was assessed by transtemporal Doppler ultrasound at the same time points. Results  l‐NMMA produced a mean reduction in ICA flow area under curve (AUC) in the control group of 12.8 ± 17.8% compared with a 2.1 ± 21.7% reduction in the group with diabetes (P